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Biomedical subjects

G W Moore

Publications and source records attributed to G W Moore.

At least 19 recordsLinked to original sources
PubMed1992

Liver cell dysplasia: a DNA aneuploid lesion with distinct morphologic features.

Liver cell dysplasia is characterized by hepatocellular foci with nuclear atypia. It is often seen in cirrhosis and may be a precursor of hepatocellular carcinoma (HCC). To determine whether liver cell dysplasia is DNA aneuploid, 72 sections of 33 cirrhotic livers from the autopsy files of The Johns Hopkins Hospital were studied, and 14 foci of dysplasia from 13 cirrhotic livers were selected. Patients ranged in age from 32 to 70 years. Histologically, there were 10 foci of low-grade dysplasia and four foci of high-grade dysplasia. Nine HCCs served as positive controls; seven autopsy livers with no morphologic or clinical evidence of primary liver disease served as negative controls. One focus of HCC and one focus of dysplasia were unsatisfactory for analysis. Flow cytometric examination demonstrated subpopulations with DNA abnormality in four of nine (44%) foci of low-grade dysplasia, of which three were aneuploid. Three of four (75%) foci of high-grade dysplasia were aneuploid. Six of eight (75%) HCCs showed DNA abnormality, of which five were aneuploid. DNA aneuploidy was not present in the seven control livers; however, one showed DNA abnormality. We conclude that liver cell dysplasia is a morphologic entity that contains DNA aneuploid cells, a feature that supports the role of liver cell dysplasia in the evolution of HCC.

Adult↗
PubMed1992

Automated review of blood donor screening test patterns at a regional blood center.

Regional blood centers recently increased the number of tests used to protect transfusion recipients from infectious disease. The Food and Drug Administration has noted that computer systems for managing these data have lost donor data or failed to recognize all deferrals. Of 118,396 consecutive donations, including 4,859 records with at least one positive test result, records were analyzed to determine the number and frequency of distinct combinations of test data. A modular precedence-logic expert system assigned donor deferrals and unit dispositions. Ten combinations of data accounted for 4,334 records (89%); the remaining 525 records (11%) were distributed among 85 combinations of test data. The expert system correctly assigned all records. Regional blood centers must interpret a growing number of test results, including donations with a complicated pattern of multiple positive screening test results. The distribution of these data is described and the expert system's ability to monitor deferrals and ensure database completeness is demonstrated.

Blood Banks↗
PubMed1992

The role of cell death in the growth of preneoplastic lesions: a Monte Carlo simulation model.

A variety of experimental and clinical examples of preneoplasia demonstrate that regression of early lesions is common. This paper examines the hypothesis that early lesions operate under the identical growth kinetics of 'late' lesions (neoplasms), but that kinetic features favouring continuous growth in established lesions tend to favour extinction of lesions composed of small numbers of cells. Growth simulations of early lesions were produced using the Monte Carlo method, a technique demanding intensive computations. With the advent of powerful personal computers, this technique is now widely available to biologists. Simulating growth under conditions of cell loss similar to those observed in established tumours, the model predicts that the great majority of initiated cell clusters are expected to reach extinction within a few cell doubling times, and most early (promoted) lesions would not likely progress to the size of a clinically detectable lesion within the life span of the host organism. These Monte Carlo simulations provide a model of initiated cell growth consistent with the recently demonstrated role of early lesion cell death in the development of human lymphomas and in transgenic mice expressing the bcl-2 oncogene. The model demonstrates that small increments in the intrinsic cell loss probability in even the earliest progenitors of malignancy can strongly influence the subsequent development of neoplasia from initiated foci.

Apoptosis↗
PubMed1992

Research by pathologists not funded by external grant agencies: a success story.

The paradigm of pathology research as an endeavor among grant-funded principal investigators resulting in first-author publications is unsupported by quantitative examination of author profiles extracted from the scientific literature. Publications in six pathology journals (Modern Pathology, American Journal of Surgical Pathology, Human Pathology, Acta Cytologica, Archives of Pathology and Laboratory Medicine, and American Journal of Clinical Pathology) and three general science journals (Science, New England Journal of Medicine, and Proceedings of the U.S. National Academy of Sciences) were reviewed. Twenty articles per journal from each of three years (1987, 1989, and 1991) were examined (a total of 520 articles). Of these, 295 articles were first-authored by a member of a department of pathology. Of the 295 articles first-authored by a member of a pathology department, 47 (16%) articles listed competitive grant support. Of the grant-supported articles, 20 articles listed NIH support, but only four had an NIH-supported principle investigator as the first author of the article. Unfunded research represented the vast majority (84%) of work produced by pathologists. A review of the ISI Citation Index showed that those articles written by funded pathologists averaged 8.7 (S.D. 7.8) citations per article, compared to 10.4 (S.D. 12.1) citations per article for unfunded pathologists. Results suggest that unfunded research accounts for the majority of pathology research activity as well as their resulting literature citations.

Authorship↗
PubMed1992

Spontaneous regression of residual tumour burden: prediction by Monte Carlo simulation.

Current cancer treatment protocols are designed to release the tumour burden down to a small number of cells. In this study, we use Monte Carlo simulations to show that small populations of cells with intrinsic cell loss rates comparable to the cell loss rates observed clinically in human tumours, may regress spontaneously. Large populations of cells tend to grow under the same conditions of cell loss that result in extinction of small clones. Furthermore, minor variations in the intrinsic cell death probability near 0.50 result in large differences in the number of surviving cells calculated at the 100th generation. When Monte Carlo simulations of clonal growth resulted in clones with large populations (> 50 cells), the population as a whole behaved in a deterministic fashion (logarithmic growth) similar to those observed in clinically observed neoplasms and consistent with other published models of tumour growth. These findings provide a plausible explanation for the clinically observed failure of tumours to recur in instances where tumour burden remains following cancer therapy. The findings also demonstrate the usefulness of the Monte Carlo method to simulate biologic events in populations where the fate of each member of a population can be modeled probabilistically.

Cell Death↗
PubMed1992

Multiparameter DNA flow cytometry of keratoacanthoma.

Keratoacanthomas (KAs) are rapidly growing cutaneous lesions that frequently look much like well-differentiated squamous cell carcinomas (SCCs) but spontaneously regress. It is uncertain whether KA is a reactive hyperplastic lesion that mimics a neoplasm or a true (but defective) neoplasm that cannot sustain progressive growth. To address this question, we performed DNA flow cytometric analysis on 14 KAs and 10 cutaneous SCCs for comparison. By multiparameter DNA flow cytometry using forward scatter and orthogonal scatter, 10 KAs and 4 SCCs had peridiploid DNA aneuploid populations (DNA indices of 1.03-1.14), and 2 SCCs had grossly aneuploid populations (DNA index, 1.69 and 2.33). Our data thus support aneuploidy in KAs. It is argued that KA is a true neoplasm.

Aneuploidy↗
PubMed1991

Ethnic differences in the anatomical location of colorectal adenomatous polyps.

The ratio of right- to left-sided colonic cancer is increasing, but data on the distribution of its usual precursor lesion, the colorectal adenoma, are contradictory. Therefore, we investigated the prevalence of right- and left-sided colorectal adenomatous polyps from January 1, 1970, to September 30, 1989, using the study design of "epidemiologic necropsy" and the autopsy files of The Johns Hopkins Hospital. Compared with the decade of the 1970's, the 1980's showed a slight decrease in the overall prevalence of right-sided adenomas (6.4 per 1,000, 95% confidence limits 4.7-8.8 vs. 5.1 per 1,000, 95% CL 3.6-6.5), but a marked decrease occurred in left-sided adenomas (11.8 per 1,000, 95% CL 9.3-14.3 vs. 6.7 per 1,000, 95% CL 4.8-8.6). As a result, the ratio of right-sided to left-sided adenomas increased from 0.55 in the 1970's to 0.77 in the 1980's. This increased ratio occurred in both sexes, although prevalences were lower in females, and in whites. Unexpectedly, blacks had a ratio of right-sided to left-sided adenomas greater than unity in both the 1970's and 1980's (1.19 vs. 1.79) due to a relatively high prevalence of right-sided adenomas (5.8 per 1,000, 95% CL 3.6-8.0 in 1970's; 5.8 per 1,000, 95% CL 3.3-8.3 in 1980's), but low prevalences of left-sided adenomas (4.9 per 1,000, 95% CL 3.0-6.8 in 1970's; 3.2 per 1,000, 95% CL 1.2-5.2 in 1980's). The overall adenoma prevalence in blacks was lower than in whites. We conclude that the right-sided predominance of colorectal adenomas in blacks suggests ethnic differences in the pathogenesis of colorectal adenomas. This observation may have important implications for secondary prevention of colorectal cancer.

Adenoma↗
PubMed1991

DNA analysis of cardiac myxomas: flow cytometry and image analysis.

Cardiac myxoma is the most common primary tumor of heart, but there is a longstanding controversy over whether it is a true neoplasm or a reactive lesion. We analyzed 24 cardiac myxomas from 22 patients: 22 by DNA flow cytometry and five by image analysis. Two myxomas were aneuploid; one of those analyzed by flow cytometry, and the other by image analysis. Proliferative fractions (S + G2/M) were high in three tumors from patients with multiple myxomas (mean, 15.9%; SD, 4.0%) as compared with 12 solitary uncomplicated myxomas (mean, 7.7%; SD, 6.0%). S-phase and proliferative fractions were low in embolic, recurrent, and solitary myxomas. The presence of aneuploidy in some myxomas supports a neoplastic origin for this tumor.

Adult↗
PubMed1991

Cell growth simulations predicting polyclonal origins for 'monoclonal' tumors.

Studies showing the clonal identity of various tumors have led to the belief that most tumors originate from a single cell. It is shown by Monte Carlo computer simulations that monoclonality can evolve from minor differences either in cell cycle time or in the probability of cell death in a polyclonal 'founder' population. If cells divide continuously without cell death (exponential clonal growth), a triclonal population with three starting cells (cell cycle times 0.9 days, 1 day and 1.1 days) converges to near-monoclonality in 100 generations. For cell cycle times of 0.9 days, 1.1 days and 1.1 days, and cell death probabilities of 0.45 and 0.46, populations tend toward monoclonality while the tumor is still small (less than 3 mm3).

Cell Cycle↗
PubMed1991

Clear cell dysplasia of the bladder. Report of a case with flow cytometric analysis.

Clear cell dysplasia of the bladder is a well-described morphologic entity that has been found in association with transitional cell carcinoma of the bladder. Its biologic role in bladder tumorigenesis is unknown, and no instances of its polidy analysis have been reported. The authors describe a case of clear cell dysplasia of the bladder found in association with a primary adenocarcinoma of the bladder. Flow cytometric analysis of bladder tissue involved by clear cell dysplasia, adenocarcinoma and cystitis cystica (all from the same bladder) demonstrated no DNA aneuploid populations. Cells from the area of clear cell dysplasia had an S + G2 + M fraction of 7%, indicating that it was a proliferative lesion. Cells from the adenocarcinoma had an S + G2 + M phase of 18%, and cells from an area of cystitis cystica had an S + G2 + M phase of 4%.

Adenocarcinoma↗
PubMed1991

Object-oriented controlled-vocabulary translator using TRANSOFT + HyperPAD.

Automated coding of surgical pathology reports is demonstrated. This public-domain translation software operates on surgical pathology files, extracting diagnoses and assigning codes in a controlled medical vocabulary, such as SNOMED. Context-sensitive translation algorithms are employed, and syntactically correct diagnostic items are produced that are matched with controlled vocabulary. English-language surgical pathology reports, accessioned over one year at the Baltimore Veterans Affairs Medical Center, were translated. With an interface to a larger hospital information system, all natural language pathology reports are automatically rendered as topography and morphology codes. This translator frees the pathologist from the time-intensive task of personally coding each report, and may be used to flag certain diagnostic categories that require specific quality assurance actions.

Algorithms↗
PubMed1991

PRELOG: precedence logic inference software for blood donor deferral.

Blood collection facilities have recently witnessed a substantial increase in the complexity of tests used to detect infectious disease in donor populations, and there is a stringent regulatory effort by the Food and Drug Administration (FDA) to validate the software for managing this information. PRELOG is precedence-based inference software used to determine a donor's suitability for continued donations and whether the donation can be released for transfusion. PRELOG accepts ternary input for test results (positive, negative, or undetermined), and solves the logic rules sequentially, so that the rulebase can be validated in a concise and consistent manner.

Blood Banks↗
PubMed1991

Basal cell carcinoma: importance of histologic discontinuities in the evaluation of resection margins.

Pathologists frequently need to judge whether basal cell carcinomas have been excised adequately. Traditionally, excision adequacy is assessed by looking for the presence of tumor at the margins of resection. This time-honored activity has questionable value, since it has been demonstrated that the majority of tumors with positive margins do not recur, and a substantial minority of tumors with negative margins do recur. It is proposed that excision adequacy can be evaluated by considering the pattern of tumor growth. Tumors composed of widely dispersed nests need wider margins than tumors that grow as tight clusters of tumor nests, and this assertion can be evaluated statistically. A morphometric study of 28 basal cell carcinomas (BCCs) was performed, in which the distribution of tumor cell nests seen in cross-section was analyzed. The average distance from the center varied greatly (272 to 2273 microns) among these tumors. Standard deviations were calculated from distances between the tumor center to each nest within the tumor, and one-tailed Student's t tests were used to obtain 90%, 95%, and 99% confidence limits for distances beyond which no additional tumor nests are expected. These distances, in tumor radii, ranged from 0.8 to 1.9 and from 1.03 to 4.89, for 90% and 99% confidence limits, respectively. Conventional methods used to determine margin adequacy do not account for the discontinuous appearance of BCC in histologic sections. This theoretical model demonstrates that an alternate way of assessing excision adequacy can be achieved with a statistical analysis of the pattern of tumor growth, rather than looking for absence of tumor at the resection margin.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal Cell Carcinoma↗
PubMed1990

[Comparison of 2 series of autopsies observed at Johns-Hopkins Medical Center, Baltimore (JHMI) and at the Neuchâtel Institute of Pathology (INAP)].

We are reporting the first results of a comparative study of 100 consecutive autopsies and their clinical diagnoses, observed at the Johns Hopkins Medical Institutions (JHMI) and at the Institut neuchâtelois d'anatomie pathologique (INAP). The diagnoses of the two series were coded according to the two different systems used currently at the two institutions. The data from Baltimore were automatically classified by a special "key word method" using the categories of the Index Medicus (MeSH = Medical subject headings). We proceeded then to a second recording by SNOMED codes, introduced into the computer system in the same way as we document the autopsy diagnoses in Neuchâtel. The two series could be compared in detail according to topographical, morphological and aetiological parameters. The over-all repartition of the examined cases shows a higher incidence of newborns in Baltimore (23), in Neuchâtel we observed only 7 newborn autopsies. The mean age was inferior in Baltimore (males: 53.5 years for JHMI, 73.1 years for INAP; females: 58.4 years for JHMI, 66.2 years for INAP). The number of diagnoses per autopsy was 31.9 at JHMI, and 50.1 in Neuchâtel. The topographical distribution of clinical and autopsy diagnoses showed a higher frequency of central nervous system lesions in JHMI which might be explained by the activity of a neuropathological division. Findings concerning the morphological categories revealed a higher frequency in JHMI for traumatic abnormalities (7.2% vs 2.5%), malformations (4.3% vs 0.8%), whereas inflammation and fibrosis and degenerative lesions were more often encountered in Neuchâtel. The differences in morphological observations could be attributed to a higher proportion of newborn cases in JHMI with complex malformation syndromes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions.

Controversy about gastric cancer risk after partial gastrectomy exists, especially in the United States. Therefore, we performed a meta-analysis to determine overall relative risk and weighted mean relative risk for subsets of postgastrectomy patients, define possible high risk patients suitable for surveillance, and assess for publication bias which would overestimate risk. If 2 studies were excluded because of heterogeneity, overall relative risk (RR) for gastric stump cancer in 22 studies analyzed was 1.66 [95% confidence limits (CL), 1.54-1.79]. With these 2 studies included, the RR summarized with a random effects model to account for study heterogeneity was 1.46 (95% CL, 1.18-1.82). No obvious evidence of publication bias was detected. Patients 15 years or more postoperative had a weighted mean RR of 1.48 (95% CL, 1.31-1.67) and patients 5-14 years postoperative had a RR of 0.91 (95% CL, 0.71-1.17) (P = 0.026). Patients operated upon for gastric ulcer had a weighted mean RR of 2.12 (95% CL, 1.73-2.59) and patients with duodenal ulcers had a RR of 0.84 (95% CL, 0.66-1.05) (P = 0.001). The weighted mean RR for females was 1.79 (95% CL, 1.39-2.29) and for males 1.43 (95% CL, 1.27-1.62) (P = 0.074). For Billroth II gastrectomy the weighted mean RR was 1.60 (95% CL, 1.15-2.18) and for Billroth I gastrectomy 1.20 (95% CL, 1.01-1.42) (P = 0.220). Although differences in risk between subsets of postagastrectomy patients seen to exist, recommendations concerning endoscopic surveillance await further studies of cost-benefit analysis.

Female↗
PubMed1990

Hepatic vascular disease and portal hypertension in polycythemia vera and agnogenic myeloid metaplasia: a clinicopathological study of 145 patients examined at autopsy.

The pathogenesis of portal hypertension arising in patients with myeloproliferative disorders has been difficult to understand because liver biopsy findings often show minimal changes. It has been suggested that increased splenic blood flow, hepatic infiltration with hematopoietic cells or sinusoidal fibrosis may be important. We have reviewed the autopsy findings and clinical histories of 97 patients with polycythemia vera and 48 patients with agnogenic myeloid metaplasia collected from three institutions and from the Polycythemia Vera Study Group. Cirrhosis was present in seven patients, one of whom had bleeding varices. Esophageal varices were present clinically in 10 patients without cirrhosis (seven polycythemia and three agnogenic myeloid metaplasia). All of these patients had lesions in small or medium-sized portal veins and four had stenosis of the extrahepatic portal vein with histology compatible with organized thrombi. Nodular regenerative hyperplasia occurred in 14.6% and correlated closely with the presence of portal vein lesions. Thirty patients had greater than 500 ml of ascites, seven of these patients also had varices and six of them had hepatic vein thrombosis. Ascites also correlated with hepatic vein disease confined to small intrahepatic branches. No correlation was seen between hepatic hematopoietic infiltration and signs of portal hypertension. We conclude that esophageal varices are common and are almost always associated with portal vein lesions visible by light microscopy. These portal vein lesions, and the secondary effects of nodular regenerative hyperplasia and portal hypertension, are most likely a result of portal vein thrombosis in patients with myeloproliferative disorders.

Adult↗
PubMed1990

Effect of machine parameters on variance display in Doppler color flow mapping.

In color Doppler flow studies, "variance" is an important display modality for diagnosing stenotic, regurgitant, and shunt lesions. Variance, a mathematical calculation based on the variation in the Doppler signal frequencies, has been reported to reflect the degree of flow disturbance. A wide-band pulsed Doppler spectrum results in a larger degree of variance. It has been suggested that variance area (green color or mosaic area) might provide useful quantitative information regarding the severity of stenotic, regurgitant, and shunt lesions. Since ultrasound machine settings may affect the color Doppler variance image, we evaluated in 101 free jet experiments the effect of packet size (eight versus four samples per line), pulse repetition frequency (3.9 versus 5.2 kHz), frame rate (11 versus 22 frames per second), system gain (+15 dB versus -15 dB), transmit power (high versus low), and moving target indicator (MTI) filter setting (high versus low) on variance display. The variance area was planimetered using an image analysis computer. The following machine parameters were inversely correlated with variance area: (1) packet size (p less than 0.01), (2) pulse repetition frequency (p less than 0.001), and (3) frame rate (p less than 0.05). Both system gain (p less than 0.001) and wall filter setting (p less than 0.01) showed a direct correlation with variance area. We conclude that machine factors must be standardized in evaluating stenotic, regurgitant, and shunt lesions by color Doppler variance display imaging.

Analysis of Variance↗